Systems for treatment of a neurological disorder using electrical nerve conduction block

ABSTRACT

One aspect of the present disclosure is a system including a waveform generator, a controller, and an electrical contact. The waveform generator is for generating an electrical nerve conduction block (ENCB). The controller is coupled with the waveform generator. The controller is configured to receive an input comprising at least one parameter to adjust the ENCB. The electrical contact is coupled with the wave-form generator. The electrical contact is configured to be placed into contact with a nerve. The electrical contact comprises a high charge capacity material that prevents formation of damaging electro-chemical products at a charge delivered by the ENCB. The electrical contact is configured to deliver the ENCB to the nerve to block transmission of a signal related to a pain through the nerve.

GOVERNMENT FUNDING

This work was supported, at least in part, by grant number R01-NS-074149and grant number R01-EB-002091 from the Department of Health and HumanServices, National Institutes of Health, National Institute ofNeurological Disorders and Stroke. The United States government may havecertain rights in this invention.

RELATED APPLICATIONS

This application claims the benefit of U.S. patent application Ser. No.14/969,826, filed Dec. 15, 2015, the entirety of which is herebyincorporated by reference for all purposes.

TECHNICAL FIELD

The present disclosure generally relates to electrical nerve conductionblock (ENCB), and more particularly to methods of treating aneurological disorder using ENCB without producing damagingelectrochemical reaction products.

BACKGROUND

Many neurological disorders are characterized by abnormal conduction inone or more nerves, leading to unwanted neural activity. In someinstances, the abnormal conduction can be associated with pain,spasticity, or other pathological effects realized by different endorgans. Examples of neurological disorders can include stroke, braininjury, spinal cord injury (SCI), cerebral palsy (CP), and multiplesclerosis (MS), as well as cancer, joint replacement, endometriosis,hyperhidrosis, vertigo, sialorrhea, torticollis, neuroma, hiccups, andthe like. Traditionally, these neurological disorders have been treatedusing drugs or invasive methods, like neurolysis. Although generally notclinically used, these neurological disorders also can be treated byblocking conduction in the peripheral axons to stop the unwanted neuralactivity through application of a high frequency alternating current(HFAC) waveform and/or a direct current (DC) waveform.

HFAC waveforms have been shown to provide a localized, immediate,complete, and reversible conduction block without causingelectrochemical damage. However, HFAC produces a transient onsetresponse in the nerve, which can take many seconds to diminish andcease. The onset response has not yet been eliminated throughmodification of the HFAC waveform or electrode design alone. While it ispossible to completely neutralize the onset response by applying a briefDC waveform through a flanking electrode, nerve conduction is lost afterseveral applications of the DC waveform. The loss of conduction may bedue to the creation of damaging electrochemical reaction products causedby the DC waveform at the levels of charge required to be injected toblock conduction in the nerve.

Additionally, DC waveforms can be used as an alternative to HFAC block.Indeed, the DC waveforms can be designed to eliminate the unfavorableonset response or anodic break excitation. However, these DC waveformscan cause electrochemical damage to the nerve. For example, the damagecan be due to the formation of damaging electrochemical reactionproducts, like free radicals, that can be created when the chargeinjection capacity of the interface is exhausted. The charge injectioncapacity (or “charge capacity”) generally refers to an amount of chargethat can be delivered by the electrode before voltage across theelectrode-electrolyte interface leaves the water-window (a voltage in acyclic voltammogram (CV) between the specific the production ofmolecular oxygen and molecular hydrogen).

SUMMARY

The present disclosure generally relates to electrical nerve conductionblock (ENCB), and more particularly to methods of treating aneurological disorder using ENCB without producing damagingelectrochemical reaction products. For example, the ENCB can bedelivered to a nerve using a therapy delivery device (e.g., anelectrode) that includes an electrode contact that includes (e.g., ismade from, coated by, or the like) a high-charge capacity materialcapable of delivering a charge required to achieve the desired block ofthe nerve without the occurrence of irreversible electrochemicalreactions. As an example, the high charge capacity material can includeplatinum black, iridium oxide, titanium nitride, tantalum,poly(ethylenedioxythiophene), of the like.

An aspect of the present disclosure includes a method for reducing painin a subject. The method includes placing an electrode contact inelectrical communication with a nerve that transmits a signal related tothe pain. The method also includes applying an ENCB to the nerve throughthe electrode contact without causing electrochemical damage to thenerve. The electrode contact can include a high charge capacity materialthat prevents formation of damaging electrochemical reaction products ata charge delivered by the ENCB. The method also includes blockingtransmission of the signal related to the pain through the nerve withthe ENCB to reduce the pain.

Another aspect of the present disclosure includes a method for reducingmuscle spasticity in a subject. The method includes placing an electrodecontact in electrical communication with a nerve that transmits a signalrelated to the muscle spasticity. The method also includes applying anENCB to the nerve through the electrode contact without causingelectrochemical damage to the nerve. The electrode contact can include ahigh charge capacity material that prevents formation of damagingelectrochemical reaction products at a charge delivered by the ENCB. Themethod also includes blocking transmission of the signal through thenerve with the ENCB to stop the muscle spasticity.

A further aspect of the present disclosure includes a method fortreating a neurological disorder (e.g., hyperhidrosis, vertigo,sialorrhea, or the like) in a subject. The method includes placing anelectrode in electrical communication with a nerve that transmits asignal related to the disorder. The method also includes applying anENCB to the nerve through the electrode contact without causingelectrochemical damage to the nerve. The electrode contact can include ahigh charge capacity material that prevents formation of damagingelectrochemical reaction products at a charge delivered by the ENCB. Themethod further includes blocking transmission of the signal through thenerve with the ENCB to treat the disorder.

A further aspect of the present disclosure includes a system comprisinga waveform generator, a controller, and an electrical contact. Thewaveform generator is for generating an electrical nerve conductionblock (ENCB). The controller is coupled with the waveform generator. Thecontroller is configured to receive an input comprising at least oneparameter to adjust the ENCB. The electrical contact is coupled with thewaveform generator. The electrical contact is configured to be placedinto contact with a nerve. The electrical contact comprises a highcharge capacity material that prevents formation of damagingelectro-chemical products at a charge delivered by the ENCB. Theelectrical contact is configured to deliver the ENCB to the nerve toblock transmission of a signal related to a pain through the nerve.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of the present disclosure will becomeapparent to those of skill in the art to which the present disclosurerelates upon reading the following description with reference to theaccompanying drawings in which:

FIG. 1 is an illustration of an example system that can deliverelectrical nerve conduction block (ENCB) to a nerve without causingelectrochemical damage.

FIGS. 2 and 3 are examples of different therapy delivery devices thatcan be used by the system shown in FIG. 1.

FIG. 4 is an illustration of an example system that can control thewaveform generator in FIG. 1 according to an input.

FIG. 5 is a process flow diagram illustrating an example method fordelivering ENCB to a nerve without causing electrochemical damage.

FIG. 6 is a process flow diagram illustrating an example method foradjusting a degree of ENCB applied to the nerve.

FIG. 7 is a cyclic voltammogram of several platinum black electrodecontacts with different Q values.

FIG. 8 is a diagram depicting one example of a system for using a DCENCB to block nerve signal transmission without damaging the nerve.

FIG. 9 is an illustrative DC block trial showing that the twitcheselicited by proximal stimulation are blocked during the blocking phaseof a trapezoidal waveform.

FIG. 10 is an illustration of the viability of sciatic nerve conductionfollowing DC ENCB.

FIG. 11 is an illustration of an example of a multi-phase DC ENCBwaveform.

FIG. 12 is an illustration of an experimental setup and an ENCB using aDC plus HFAC no-onset blocking waveform.

FIG. 13 is an illustration of the DC delivery with a pre-charge pulse, ablocking phase of opposite polarity and a final recharge phase.

FIG. 14 is an illustration of the effect of electric nerve conductionblock waveforms on evoked gastronomies muscle forces, illustrating thatdifferent amplitudes of DC block will block different percentages of theHFAC onset response.

FIGS. 15 and 16 each illustrate the use of different slopes and multipletransitions in the DC waveform to avoid activating a muscle as thecurrent level is varied..

FIG. 17 illustrates a DC block that is too short to block the entireHFAC onset response.

FIG. 18 is a schematic illustration showing non-limiting examples ofpotential clinical applications for ENCB.

DETAILED DESCRIPTION I. Definitions

Unless otherwise defined, all technical terms used herein have the samemeaning as commonly understood by one of ordinary skill in the art towhich the present disclosure pertains.

In the context of the present disclosure, the singular forms “a,” “an”and “the” can also include the plural forms, unless the context clearlyindicates otherwise.

The terms “comprises” and/or “comprising,” as used herein, can specifythe presence of stated features, steps, operations, elements, and/orcomponents, but do not preclude the presence or addition of one or moreother features, steps, operations, elements, components, and/or groups.

As used herein, the term “and/or” can include any and all combinationsof one or more of the associated listed items.

Additionally, although the terms “first,” “second,” etc. may be usedherein to describe various elements, these elements should not belimited by these terms. These terms are only used to distinguish oneelement from another. Thus, a “first” element discussed below could alsobe termed a “second” element without departing from the teachings of thepresent disclosure. The sequence of operations (or acts/steps) is notlimited to the order presented in the claims or figures unlessspecifically indicated otherwise.

As used herein, the terms “nerve block”, “nerve conduction block”, and“block” can be used interchangeably when referring to the failure ofimpulse transmission at some point along a nerve. In some instances,nerve conduction can be blocked by extinguishing an action potential atsome point as it travels along the nerve. In other instances, nerveconduction can be blocked by increasing the activation threshold of atarget nerve and/or decreasing the conduction velocity of a nerve, whichcan lead to an incomplete or substantial block of nerve conduction.

As used herein, nerve conduction is “blocked” when transmission ofaction potentials through a nerve is extinguished completely (e.g., 100%extinguished).

As used herein, nerve conduction is “substantially blocked” when an“incomplete nerve block” or “substantial nerve block” occurs. The terms“incomplete block” and “substantial block” can refer to a partial block,where less than 100% (e.g., less than about 90%, less than about 80%,less than about 70%, less than about 60%, or less than about 50%) of theaction potentials traveling through a nerve are extinguished.

As used herein, the term “electrical nerve conduction block” or “ENCB”can refer to an external electrical signal (or waveform) that cangenerate an electric field sufficient to block the conduction in anerve. The ENCB can include a direct current (DC) waveform (balancedcharge biphasic, substantially balanced-charge biphasic, or monophasic)and/or a high frequency alternating current (HFAC) waveform.

As used herein, the term “DC waveform” can refer to a waveform that caninclude a current pulse of either polarity (e.g., either cathodic oranodic). In some instances, the DC can be applied as the first phase ofa biphasic waveform. The second phase of the biphasic waveform caneither reverse 100% of the total charge delivered by the first phase (asa charge-balanced biphasic waveform) or reverse less than 100% of thetotal charge delivered by the first phase, thereby reducing theproduction of damaging reaction products that can cause damage to thenerve and/or the electrodes used to deliver the DC. In other instances,the DC can be applied as a monophasic waveform.

As used herein, the term “high frequency” with reference to alternatingcurrent (e.g. HFAC) can refer to frequencies above approximately onekiloHertz (kHz), such as about 5 kHz to about 50 kHz.

As used herein, the term “electrical communication” can refer to theability of an electric field to be transferred to a nerve and have aneuromodulatory effect (e.g. blocking neural signal transmission) withinthe nerve of a patient.

As used herein, an “electrical signal” (e.g., either voltage controlledor current controlled) can be applied to the axon, cell body ordendrites of a nerve (or population of nerves) so long as signaltransmission (or conduction of action potentials) is blocked and theneural tissue is not damaged.

As used herein, the term “signal transmission” when associated with anerve can refer to the conduction of action potentials within the nerve.

As used herein, the term “therapy delivery device” can refer to a deviceconfigured to deliver an ENCB to a nerve. In some examples, the therapydelivery device can include an electrode with one or more contacts. Theone or more contacts can be made of a high charge capacity material thatprovides the conversion of current flow via electrons in a metal(wire/lead) to ionic means (in an electrolyte, such as interstitialfluid). In some instances, the electrode can aid in shaping the electricfield generated by the contact(s). As an example, the electrode can beimplantable and/or positioned on a skin surface of a patient.

As used herein, the term “high charge capacity material” can refer to amaterial that allows an electrode contact to deliver a charge necessaryto block conduction in at least a portion of a nerve without damagingthe nerve.

As used herein, the term “Q-value” can refer to a value of the totalamount of charge that can be delivered through an electrode contactbefore causing irreversible electrochemical reactions, which can causethe formation of damaging reaction products. For example, the highcharge capacity material can have a large Q-value, which enables a largecharge to be delivered through the electrode contact before causingirreversible electrochemical reactions.

As used herein, the term “damaging reaction products” can refer toreactions that can damage the nerve, another part of the body inproximity to the electrode contact, and/or the electrode contact. Forexample, a damaging reaction product can be due to oxygen evolution orhydrogen evolution. As another example, a damaging reaction product canbe due to dissolution of the material of an electrode contact. As usedherein, an ENCB can be considered “safe” when the block occurs withoutproducing damaging reaction products.

As used herein, the term “electrode/electrolyte interface” can refer toa double layer interface where a potential difference is establishedbetween the electrode and the electrolyte (e.g., an area of thepatient's body, such as interstitial fluid).

As used herein, the term “geometric surface area” of an electrodecontact can refer to a two-dimensional surface area of the electrodecontact, such as a smooth surface on one side of the electrode contactas calculated by the length times the width of the two-dimensional outersurface of the electrode contact.

As used herein, the terms “effective surface area” and “true surfacearea” of an electrode contact can refer to the surface area that can beinferred from the area within the curve of a cyclic voltammogram (“CV”)of the electrode contact.

As used herein, the term “waveform generator” can refer to a device thatcan generate an electric waveform (e.g., charge balanced biphasic DC,substantially charge balanced biphasic DC, monophasic DC, HFAC, or thelike) that can be provided to an electrode contact to provide an ENCB.The waveform generator can be, for example, implantable within apatient's body and/or external to the patient's body.

As used herein, the term “nervous system” refers to a network of nervecells and neural tissue that transmit electrical impulses (also referredto as action potentials) between parts of a patient's body. The nervoussystem can include the peripheral nervous system and the central nervoussystem. The peripheral nervous system includes motor nerves, sensorynerves, and autonomic nerves, as well as interneurons. The centralnervous system includes the brain and the spinal cord. The terms “nerve”and “neural tissue” can be used interchangeably herein to refer totissue of the peripheral nervous system or the central nervous systemunless specifically described as referring to one, while excluding theother.

As used herein, the terms “disorder” and “neurological disorder” can beused interchangeably to refer to a condition or disease characterized atleast in part by abnormal conduction in one or more nerves. In someinstances, the abnormal conduction can be associated with pain and/orspasticity. Examples of neurological disorders can include stroke, braininjury, spinal cord injury (SCI), cerebral palsy (CP), and multiplesclerosis (MS), as well as cancer, joint replacement, endometriosis,hyperhidrosis, vertigo, sialorrhea, torticollis, neuroma, hiccups, andthe like.

As used herein, the terms “patient” and “subject” can be usedinterchangeably and refer to any warm-blooded organism suffering from aneurological disorder. Example warm-blooded organisms can include, butare not limited to, a human being, a pig, a rat, a mouse, a dog, a cat,a goat, a sheep, a horse, a monkey, an ape, a rabbit, a cow, etc.

II. Overview

The present disclosure generally relates to electrical nerve conductionblock (ENCB). The ENCB can block signal transmission (also referred toas “conduction” of action potentials) in one or more nerves to stopunwanted neural activity of a neurological disorder, such as pain,muscle spasticity, hyperhidrosis, vertigo, sialorrhea, and the like.However, traditionally, ENCB has not been utilized to treat unwantedneural activity in such neurological disorders. One reason for thereluctance to use ENCB is an occurrence of undesirable side effects,such as the generation of dangerous electrochemical reaction products.The high charge capacity electrode contacts of the present disclosurecan substantially eliminate this electrochemical damage at charges usedfor the ENCB. Accordingly, the present disclosure relates to methods oftreatment of a neurological disorder using ENCB without causingelectrochemical damage to the nerve, the patient's body, or theelectrode.

The ENCB can be delivered to a nerve using a therapy delivery device(e.g., an electrode) that includes an electrode contact comprising ahigh-charge capacity material. Using the high charge capacity material,the electrode contacts of the present disclosure can deliver the ENCBwithout the onset response characteristic of HFAC waveforms and alsowithout the electrochemical damage due to application of DC waveforms.Generally, the high-charge capacity electrode can have a Q value aboveabout 100 μC. In other words, the high-charge capacity electrode candeliver a charge above about 100 μC without the generation ofirreversible reaction products. However, in some instances, thehigh-charge capacity electrode can have a Q value between about 1 μC andabout 100 μC . In other instances, the high-charge capacity electrodecan have a Q value on the order of about 10 μC.

Using the high-charge capacity material, more charge can be deliveredsafely for longer periods of time compared to traditional stimulationelectrodes, such as those fabricated from platinum or stainless steel.In certain instances, the high-charge capacity material can have acharge injection capacity (the charge density that safely can bedelivered through the material) of about 1 to about 5 mC/cm². Incomparison, polished platinum, a non-high charge capacity material, hasa charge injection capacity of about 0.05 mC/cm². With an electrodecontact comprising a high charge capacity material, the effectivesurface area of the electrode contact is increased by several orders ofmagnitude over the geometric surface area. As such, as an example, DCcan be safely delivered through monopolar nerve cuff electrode contactsfor durations as long as ten seconds without any nerve damage.Accordingly, the present disclosure provides a superior block that iseffective, reversible, and “no onset”.

III. Systems

In some aspects, the present disclosure relates to a system 10 (FIG. 1)that can be used to treat a neurological disorder by blocking signaltransmission through at least a portion of a target nerve associatedwith the disorder. The system 10 can apply an electrical nerveconduction block (ENCB) to the nerve to block the signal transmission inthe nerve. Advantageously, the ENCB can be delivered at the requiredcharge levels without causing the generation of electrochemical reactionproducts that cause electrochemical damage. For example, the ENCB can beused for motor nerve block, sensory nerve block, autonomic nerve block,block in the central nervous system, block of interneurons, or the like.As opposed to other types of block, like neurolysis, when the ENCB is nolonger applied, normal conduction is restored to the nerve.

The system 10 can include a waveform generator 12 coupled to (e.g.,through a wired connection or a wireless connection), and in electricalcommunication with, a therapy delivery device 14 that includes one ormore electrode contacts 16. The waveform generator 12 can generate anelectrical waveform (also referred to as an “ENCB waveform” or simply“ENCB”) that can be used to block signal transmission through the nerve.In some instances, the electrical waveform can be a monophasic directcurrent (DC) waveform, a balanced charge biphasic DC waveform, and/or asubstantially balanced charged biphasic DC waveform. In other instances,the waveform can be a high frequency alternating current (HFAC)waveform.

The therapy delivery device 14 can receive the generated electricalwaveform and deliver the ENCB to a nerve (also referred to as “targetnerve” or “neural tissue”) through one or more electrode contacts 16(monopolar and/or bipolar). For example, the waveform generator 12 cangenerate different waveforms to be applied at different times and/orthrough different electrode contacts. As an example, the waveformgenerator 12 can generate both a DC waveform and an HFAC waveform to beapplied at different times, As another example, the waveform generator12 can generate a plurality of DC waveforms with different timingcharacteristics to be applied by different electrode contacts 16.

The therapy delivery device 14 is able to deliver the ENCB without theformation of irreversible, damaging electrochemical reaction products atleast because the one or more electrode contacts 16 can include a highcharge capacity material. Generally, the high charge capacity materialcan be any material that can allow the electrode contact 16 to deliveran electric charge required for the desired nerve conduction blockwithout forming irreversible and damaging reaction products. Forexample, the water window of the high charge capacity material can bewidened so that the charge required for the block can be deliveredwithout achieving hydrogen or oxygen evolution. Non-limiting examples ofhigh charge capacity materials include platinum black, iridium oxide,titanium nitride, tantalum, poly(ethylenedioxythiophene), and suitablecombinations.

In some examples, the one or more electrode contacts 16 can befabricated from the high charge capacity material. In other examples,the one or more electrode contacts 16 can include an electricallyconductive material (e.g., platinum, stainless steel, or the like) thatis coated, at least in part, by the high charge capacity material. Instill other examples, the one or more electrode contacts 16 can includeboth electrode contacts fabricated from the high charge capacitymaterial and electrode contacts coated, at least in part, by the highcharge capacity material. In further examples, the one or more electrodecontacts 16 can include both contacts that include the high chargecapacity material and other contacts that do not include the high chargecapacity material.

In one example, the one or more electrode contacts 16 can have ageometric surface area of at least about 1 mm². In another example, thegeometric surface area of one or more electrode contacts 16 can bebetween about 3 mm² to about 9 mm². In some examples, each of the one ormore electrode contacts 16 can have about equal geometric surface areas.In other examples, the one or more electrode contacts 16 can havedifferent geometric surface areas.

In some instances, the therapy delivery device 14 can be an electrode.In certain non-limiting examples, the therapy delivery device 14 can bean electrode (e.g., a nerve cuff electrode shown in FIG. 2 or a flatinterface nerve electrode (FINE) shown in FIG. 3) that includes aplurality of multiple contiguous electrode contacts 16. However, thetherapy delivery device 14 can have other configurations, which are notshown, such as a helical cuff or other nerve cuff electrode, a mesh, alinear rod-shaped lead, paddle-style lead, a disc contact electrodeincluding a multi-disc contact electrode, or a penetrating intraneuralelectrode.

Shown in FIG. 4 is an example system 40 that can control the parametersof the electrical waveform generated by the waveform generator 12. Thesystem 40 can include a controller 42 that can receive an input(including at least one parameter) and signal the waveform generator 12to adjust and/or deliver the electrical waveform to the therapy deliverydevice 14 so that an appropriate ENCB can be delivered to the nerve. Forexample, based on the input, the controller 42 can specify a timingparameter, an intensity parameter, a waveform parameter, and/ordesignate which of the one or more electrode contacts 16 is to deliverthe ENCB. In one example, the controller 42 can specify an intensityparameter so that a portion of the signal transmission through the nerveis stopped (also referred to as “adjusting a degree of the block”). Byblocking only a portion of the signal transmission, a negative result ofthe signal transmission can be reduced or eliminated, while stillallowing the signal transmission through the rest of the nerve (such asallowing voluntary movement of a muscle, while blocking spasticity ofthe muscle).

In some instances, the controller 42 can be part of an open loop controlsystem, in which the input is a user input from a patient (which can bebounded by a range of “safe” parameters predefined by a medicalprofessional) or a medical professional. For example, the input can bemade via an analog device (like a switch, dial, or the like), allowingthe user to input an analog value. As another example, the input can bemade via a digital device (like a keyboard, microphone, or the like),which can allow the user to input a digital value. The controller 42 caninterpret the input and signal the waveform generator 12 including aparameter adjusted based on the input.

In other instances, the controller 42 can be part of a closed loopcontrol system that can receive the input from an entity other than auser. For example, the closed loop control system can employ one or moresensors that can sense a change in a physiological parameter. The inputcan be based on the sensed change. The controller 42 can interpret theinput and signal the waveform generator 12 including a parameteradjusted based on the input.

IV. Methods

Another aspect of the present disclosure can include methods that can beused to treat a neurological disorder by blocking signal transmissionthrough at least a portion of a nerve associated with the neurologicaldisorder with electrical nerve conduction block (ENCB). The ENCB can beapplied via a monophasic direct current (DC) waveform, a balanced chargebiphasic DC waveform, and/or a substantially balanced charged biphasicDC waveform. As another example, the ENCB can include a high frequencyalternating current (HFAC) waveform. Advantageously, the ENCB can beapplied without causing negative side effects, such as electrochemicaldamage at levels of charge injection required for the ENCB.

An example of a method 50 for delivering ENCB to a nerve without causingelectrochemical damage is shown in FIG. 5. An example of a method 60 foradjusting a degree of ENCB applied to a nerve is shown in FIG. 6. Themethods 50 and 60 can be applied, for example, using the systems asshown in FIGS. 1 and 4. The methods 50 and 60 of FIGS. 5 and 6,respectively, are illustrated as process flow diagrams with flowchartillustrations. For purposes of simplicity, the methods 50 and 60 areshown and described as being executed serially; however, it is to beunderstood and appreciated that the present disclosure is not limited bythe illustrated order as some steps could occur in different ordersand/or concurrently with other steps shown and described herein.Moreover, not all illustrated aspects may be required to implement themethods 50 and 60.

Referring now to FIG. 5, illustrated is an example of a method 50 fordelivering ENCB to a nerve without causing electrochemical damage. At52, electrode contacts of a therapy delivery device (e.g., the one ormore electrode contacts 16 of the therapy delivery device 14) can beplaced in electrical communication with a nerve that transmits a signalrelated to a neurological disorder. At least one of the electrodecontacts can include (e.g., be constructed from, coated with, or thelike) a high charge capacity material. The high charge capacity materialallows the electrode contacts to deliver the charge required forconduction block without forming irreversible and damaging reactionproducts. For example, the high charge capacity material can allow theelectrode to deliver at least 100 □C before irreversible electrochemicalreactions take place in the material. However, in some instances, thehigh-charge capacity electrode can have a Q value between about 1 μC andabout 100 μC. In other instances, the high-charge capacity electrode canhave a Q value on the order of about 10 μC. Non-limiting examples ofhigh charge capacity materials include platinum black, iridium oxide,titanium nitride, tantalum, poly(ethylenedioxythiophene), and suitablecombinations.

At 54, an ENCB can be applied through at least one of the contactswithout causing electrochemical damage to the nerve. In other words, thehigh charge capacity material enables the one or more contacts todeliver the charge required to block the conduction in the nerve withoutundergoing irreversible electrochemical reactions, and thereby damagingreaction products. At 56, transmission of a signal related to theneurological disorder (e.g., conduction of action potentials) can beblocked to treat the neurological disorder. The ENCB is reversible, sothat when transmission of the ENCB is stopped, normal signaltransmission through the nerve can be restored.

Referring now to FIG. 6, illustrated is an example of a method 60 foradjusting a degree of ENCB applied to a nerve. At 62, an ENCB (e.g.,generated by a waveform generator 12 at a first level with firstparameters) can be applied to a nerve (e.g., by therapy delivery device14) to block transmission of a signal related to a neurological disorder(e.g., conduction of action potentials) through the nerve. At 64, aninput (e.g., an input to controller 42) can be received. The input canbe from a user (e.g., a patient, a medical professional, or the like) orcan be automated (e.g., from one or more sensors that detect one or morephysiological parameters). In other words, method 60 can be operated asopen loop control and/or closed loop control. At 66, the ENCB can beadjusted (e.g., one or more parameters of the ENCB) can be adjusted toblock a portion of the transmission of the signal. In other words, theENCB can be adjusted so that only a portion of action potentials throughthe nerve (or population of nerves) are blocked from conducting, whileanother portion of action potentials is permitted to conduct through thenerve.

V. Examples—Electrode Construction and Waveform Design

The following examples illustrate construction of high charge capacityelectrode contacts, as well as the design of various waveforms that canbe delivered by the electrode contacts without causing nerve damage. Theelectrode contacts can deliver ENCB to any nerve (including peripheralnerves and/or central nervous system structures) by transmitting adesired electrical electric field trough the tissue to a desired neuralstructure. Specific waveforms are described as examples, but it will beunderstood that the waveform used for the ENCB in practice can include adirect current waveform (e.g., balanced charge biphasic, substantiallybalanced-charge biphasic, or monophasic) and/or a high frequencyalternating current (HFAC) waveform.

High Charge Capacity Electrode Contacts

In this example, electrode contacts were fabricated from high chargecapacity (“Hi-Q”) materials to achieve ENCB without causingelectrochemical damage to the nerve. The Hi-Q materials resulted in asignificant increase of the electrode contact's charge injectioncapacity, quantified in the Q-value, which can be defined as the amountof charge that the electrode contact is capable of delivering beforeirreversible electrochemical reactions take place in or due to thematerial. One example of a Hi-Q material used in this experiment isplatinized Pt (also referred to as platinum black). The platinized Pt isshown to be able to deliver DC nerve block to a nerve without causingelectrochemical damage to the nerve, even after a large number(e.g., >100) of repeated applications.

Platinized Pt electrode contacts were constructed as follows. Monopolarnerve cuff electrode contacts were manufactured using platinum foil.These electrode contacts were then platinized in chloroplatinic acidsolutions to create platinum black coatings of various roughness factorsfrom 50 to over 600. A cyclic voltammogram for different platinum blackelectrode contacts was generated in 0.1M H₂SO₄ (shown in FIG. 7) todetermine the water window, and thereby the amount of charge that can besafely delivered, for the platinized Pt.

The amount of charge that could be safely delivered by the platinized Ptelectrode contacts (the Q value) was estimated by calculating the chargeassociated with hydrogen adsorption from −0.25V to +0.1V vs. a standardAg/AgCl electrode contact. Typically Q values for these platinized Ptelectrode contacts ranged from 2.9 mC to 5.6 mC. In contrast, a standardPt foil electrode contact has a Q value of 0.035 mC.

Acute experiments were performed on Sprague-Dawley rats to test theefficacy of DC nerve block with both the platinized Pt electrodecontacts and the control Pt electrode contacts. Under anesthesia, thesciatic nerve and the gastronomies muscle on one side was dissected.Bipolar stimulating electrode contacts were placed proximally anddistally on the sciatic nerve. The proximal stimulation (PS) elicitedmuscle twitches and allowed the quantification of motor nerve block. Thedistal stimulation also elicited muscle twitches, which were comparedwith those from PS as a measure of nerve damage under the DC monopolarelectrode contact. The monopolar electrode contact was placed betweenthe two stimulating electrode contacts as schematically illustrated inFIG. 8.

A current-controlled waveform generator (Keithley Instruments, Solon,Ohio) was used to create the DC waveform. The waveform was biphasic,including a trapezoidal blocking phase followed by a square rechargephase as depicted in the lower graph (B) of FIG. 9. The ramp up and downensured that there was no onset firing from the DC. The DC parameterswere chosen so that the total charge delivered was less than the Q valuefor a given electrode contact. Each cathodic (blocking) pulse was thenfollowed by a recharge phase in which 100% of the charge was returned tothe electrode contact by an anodic pulse maintained at 100 μA.

The platinized Pt electrode contacts achieved a conduction block, whilemaintaining the total charge below the maximum Q value for eachelectrode contact. FIG. 9 illustrates a trial where complete motor nerveblock was obtained using the DC waveform with a peak amplitude of 0.55mA. The muscle twitches elicited by PS were completely blocked duringthe plateau phase of the DC delivery, as shown in the upper graph (A) ofFIG. 9.

FIG. 10 illustrates the effects of cumulative dosages of DC for five ofthe platinized Pt electrode contacts as compared to a standard platinumelectrode contact. DC was delivered as shown in FIG. 9 (lower subplot).Each cycle of DC was followed by PS and DS to produce a few twitches(not shown in FIG. 10). The PS/DS ratio is a measure of acute nervedamage. If the nerve is conducting normally through the region under theblock electrode contact, the ratio should be near one. The platinumelectrode contact demonstrated nerve damage in less than one minuteafter delivery of less than 50 mC and the nerve did not recover in thefollowing 30 minutes. The platinized Pt electrode contacts do not showsigns of significant neural damage for the duration of each experiment,up to a maximum of 350 mC of cumulative charge delivery. Similar resultswere obtained in repeated experiments using other platinized Ptelectrode contacts with variable Q values.

Multi-Phase DC Waveform ENCB

In one example, the ENCB waveform includes a multi-phase DC. As shown inFIG. 11, the multi-phase DC can include a cathodic DC phase and areciprocal anodic DC phase that are continuously cycled amongst fourcontiguous monopolar electrode contacts so that there will be acontinuous neural block without neural damage. In some instances, themulti-phase DC can be charge balanced or substantially charge balancedso that stored charge was retrieved after the blocking time by invertingthe current drive and charge-balancing the Helmholtz Double Layer (HDL).

It will be understood that the cathodic DC need not be applied first. Assuch, a multi-phase DC can be applied to the neural tissue includingapplying an anodic DC current and then a reciprocal cathodic DC current.One phase of the DC is configured to produce a complete, substantiallycomplete, or even partial nerve block and the other phase is configured(e.g. by reversing the current) to reduce or balance a charge returnedto the therapy delivery device. An exemplary multi-phase DC includesrelatively slow current ramps that fail to produce an onset response inthe neural tissue.

For example, with reference to FIG. 11, illustrated are multi-phase DCwaveforms having a substantially trapezoidal delivered by four electrodecontacts (“1,” “2,” “3,” and “4”) of a therapy delivery device. Each ofthe cathodic and anodic DC phases begins and ends with a ramp, whichprevents or substantially prevents any axonal firing. At the plateau ofthe cathodic DC phase, for example, there is complete neural block. Asdiscussed above, the cathodic DC phase can cause neural block and,following this phase, the current is reversed (anodic DC phase) tobalance the charge delivered by the therapy delivery device. The anodicrecharge time can be about equal to, or moderately longer than thecathodic block time. Moreover, the cycles of cathodic block and anodicrecharge can be applied to the neural tissue sequentially for prolongedperiods of time without any neural damage. Again, the sequence of the DCphases can be reversed and the anodic DC phase may cause the neuralblock and the cathodic DC phase may balance the charge delivered by thetherapy delivery device.

In some instances, the cathodic DC phase is conducted as follows. A DChaving a first DC amplitude can be applied to the neural tissue. Thefirst DC is then increased, over a first period of time, to a second DCamplitude. The DC having the first amplitude is insufficient to producea partial or complete neural block. Next, the second DC amplitude issubstantially maintained over a second period of time that is sufficientto produce a complete neural block. After the second period of time, thesecond DC amplitude is decreased to a third DC amplitude that is equalto, or about equal to, the first DC amplitude.

In some examples, the total net charge delivered by any of the electrodecontacts can be equal to, or about equal to zero. Advantageously,delivery of a net zero charge is considerably safer to neural tissue.However, due to external factors that lead to the entire charge notbeing delivered by the first phase, the waveforms need not be entirelycharge balanced, and instead need only be substantially charge balanced.

Application of DC and HFAC

In another example, the ENCB can include a combined delivery of DC andHFAC waveforms to reduce or eliminate an “onset response” (due to theHFAC) without causing electrochemical damage (due to the DC). HFAC hasbeen demonstrated to provide a safe, localized, reversible, electricalneural conduction block. HFAC, however, produces an onset response ofshort but intense burst of firing at the start of HFAC. Use of shortdurations of DC to block the neural conduction during this HFAC onsetphase can eliminate the onset problem, but DC can produce neural block,it can cause damage to neural tissue within a short period of time.Using a Hi-Q DC electrode contact can reduce or eliminate the damagecaused by the DC due to the formation of damaging electrochemicalreaction products.

Using a combination of a Hi-Q DC electrode contact and a HFAC electrodecontact, successful no-onset block was demonstrated, as shown in FIGS.12 A-C. FIG. 12A shows an example of an experimental setup that can beused to apply DC and HFAC to a nerve. Application of the HFAC aloneleads to an onset response, as shown in FIG. 12C. However, when a DC isapplied before the HFAC, as shown in FIG. 12B, the block is achievedwithout the onset response. In experiments with this method, more thanfifty successive block sessions without degrading nerve conduction wasachieved. DC block (at 2.4 mA) was repeatedly applied over the course ofapproximately two hours for a cumulative DC delivery of 1500 secondswith no degradation in nerve conduction. FIG. 12B (compared to FIG. 12C)shows the successful elimination of the onset response using thecombination of HFAC and Hi-Q DC nerve block.

One example use of a combined HFAC and Hi-Q DC nerve block allows the DCto be delivered for a period of time sufficient to block the entireonset response of the HFAC. This typically lasts 1 to 10 seconds, andthus the DC should be delivered for that entire period. A method offurther extending the total plateau time over which the DC can be safelydelivered is to use a “pre-charge” pulse, as shown in FIG. 13. Thepre-charge pulse comprises delivering a DC wave of opposite polarityfrom desired block effect for a length of time up to the maximum chargecapacity of the electrode contact. The DC polarity is then reversed toproduce the block effect. However, the block can now be delivered longer(e.g., twice as long) because the electrode contact has been“pre-charged” to an opposite polarity. At the end of the prolonged blockphase, the polarity is again reversed back to the same polarity as thepre-charge phase, and the total charge is reduced by delivery of thisfinal phase. In most cases, the total net charge of this waveform willbe zero, although beneficial effects can be obtained even if the totalnet charge is not completely balanced.

Varying the level of DC can partially or fully block the onset responsefrom the HFAC, as shown in FIGS. 14 A-B. FIG. 14A is a graphillustrating that application of HFAC alone results in a large onsetresponse before muscle activity is suppressed. FIG. 14B is graphillustrating that a ramped DC waveform reduces the twitches evoked by PSand minimized the onset response caused by the HFAC waveform. The barbelow the “HFAC” indicates when it is turned on. The bar under “DC”indicates when the DC is ramped from zero down to the blocking level andthen back to zero again (zero DC is not shown). This can be useful toassess the nerve health by verifying a small response even in the midstof significant nerve block. The depth of the DC block can be assessedthrough this method.

Multi-Slope transitions may help avoid onset response, especially withdiscrete changes in DC-current-amplitude over time (slope) in areal-world device. This is shown in FIGS. 15 and 16, which are resultsfrom a rat's sciatic nerve. In these examples, the DC begins with a lowslope to prevent firing of the nerve at low amplitudes. The slope canthen be increased to reach the blocking amplitude quicker. Once DC blockamplitude has been achieved, block is maintained for the durationrequired to block the HFAC onset response. The HFAC is turned on oncethe DC has reached blocking plateau. The HFAC is turned on at theamplitude necessary to block. Once the onset response has completed, theDC is reduced, initially rapidly and then more slowly in order toprevent activation of the nerve. The DC is then slowly transitioned tothe recharge phase where the total charge injection is reduced. In thisexample, the recharge phase is at a low amplitude and lasts for over 100seconds. HFAC block can be maintained throughout this period and canthen be continued beyond the end of the DC delivery if continued nerveblock is desired. Once the total period of desired block has beencompleted (which could be many hours in some cases), the HFAC can beturned off and the nerve allowed to return to normal conductingcondition. This process can be repeated again and again as needed toproduce nerve block on command as desired to treat disease.

FIG. 17 shows that the DC is maintained throughout the period of theonset response from the HFAC in order to block the entire onsetresponse. In this example (rat sciatic nerve), the onset response lastsabout 30 seconds. The DC waveform (blue trace) initially blocks theonset response, but when the DC ramps back to zero, the onset responsebecomes apparent (at ˜50 seconds). This illustrates very long DCblocking waveforms to combine the HFAC and DC blocks to achieve ano-onset block.

VI. Examples—Potential Clinical Applications

The electrode and waveform design described above can be used in manydifferent clinical applications to treat a neurological disorder usingENCB (applied to any peripheral nerve or central nervous systemstructure) without producing damaging electrochemical reaction products.The ENCB can be reversible, so that when the ENCB is turned off,conduction can be restored in the stimulated nerve.

ENCB can be used to treat a number of different neurological disordersin a patient. For example, FIG. 18 shows that different types of ENCBcan be applied in different ways to different nerves to treattorticollis (e.g., open loop control), neuroma pain (open loop control),hiccups (e.g., closed loop control), and spasticity/joint contractures(e.g., open loop control or closed loop control). Other example uses ofENCB include treatment of pain (e.g., cancer pain, back pain, jointreplacement pain, endometriosis pain, and other types of pain),hyperhidrosis, vertigo, and sialorrhea. Still other examples uses ofENCB include relaxation of the urethral sphincter and mitigatingintractable hiccups. Treatment of each of these neurological disorderscan be accomplished by applying one or more waveforms (DC and/or HFAC)through an electrode contact (of a cuff electrode, placed beside anerve, or of an external electrode, for example) without negative sideeffects by using electrode contacts that include the high chargecapacity material, as described above. In addition, in some instances,the ENCB can be combined with other types of nerve block, such aspharmacological block or thermal block (involving heating or cooling ofthe nerve), to facilitate the treatment of these neurological disorders.

Spasticity

ENCB can be used to reduce or eliminate muscle spasticity or spasms forthe purpose of preventing or reversing joint contractures. This isparticularly applicable to diseases like cerebral palsy, stroke, andmultiple sclerosis, as well as spinal cord injury and post-orthopedicsurgery. In each of these cases, muscle spasticity and spasms can be asignificant co-morbidity, causing joints to contract and remaincontracted when the patient desires to relax. Over time, suchcontraction can lead to a physiologic shortening of the contractedmuscles, causing permanent joint contractures and loss of range ofmotion in the joint. When these contractures occur, traditionaltreatments are often destructive and irreversible with often pooroutcomes. For example, traditional treatment methods involve damagingnerve fibers, either chemically or surgically, or surgical sectioning oftendons.

In contrast, ENCB, advantageously, can be applied to block spasticsignals on motor or sensory nerves, causing the muscles to relax. Insome instances, the ENCB can be applied using an open loop controlsystem, where a patient is given a switch or other input device to turnthe block on and off and to control the degree of block.

ENCB is reversible, allowing patients to relax the muscles as desired,yet reverse the block when necessary. For example, ENCB can be appliedduring periods of rest at night or when the individual is less active,allowing the muscles to fully relax, but shut off (reversed) when theindividual is active. Since the treatment with ENCB is not destructive,so the treatment can be performed much earlier in the diseaseprogression progress, therefore preventing contractures from occurring.

In some instances, the ENCB can be used to produce a partial nerveblock, which can be beneficial with preserving motor function. In apartial block, some, but not all, of the neural signals to the musclefibers are blocked and the muscle contraction strength is lessened. Thiscan allow voluntary movements of the spastic muscle without triggeringthe overpowering contraction that is common to spastic muscles. In thiscase, antagonist muscles can be strong enough to move the joint throughthe full range of motion.

An example application of ENCB is for prevention/treatment ofcontractures in spastic cerebral palsy. Spastic ankle plantar flexorsand hip adductors in cerebral palsy result in a characteristic patternof contractures that limit function, make hygiene difficult and canbecome painful. Release of gastronomies tightness through tendonlengthening or neurolysis is usually only performed as a last resort dueto the irreversible nature of these procedures. In some instances,reversible ENCB can be applied to the oburator nerve to relax the hipabductors and to the posterior tibial nerve to block ankleplantarflexion. The ENCB can be applied for many hours throughout theday, with the patient able to turn off the block when movement isdesired. Another examples application of ENCB is torticollis, which canbe used to treat/prevent involuntary movements and spasticity that occurin conditions such as dystonias, choreas and tics by blocking thesternocleidomastoid muscle and, in some cases, block of the posteriorneck muscles.

The ENCB can be accomplished through multiple methods. In someinstances, charge balanced or imbalanced HFAC waveforms (voltagecontrolled or current controlled) can be used to produce arapidly-induced and rapidly-reversible nerve conduction block. Typicalwaveform frequencies can be between 5 and 50 kHz. The waveform can becontinuous or interrupted, and each pulse can have a varied shape,including square, triangular, sinusoidal, or the like.

In other instances, charge balanced DC waveforms consisting of anincrease to a plateau of one polarity, which can last for a time period(e.g., 10 seconds), followed by a decrease of the current to an oppositepolarity, can be used for the ENCB. The plateaus of each phase can bethe same, but typically the second phase is 10-30% of the amplitude ofthe first phase. The total charge delivery is zero or substantially lessthan the charge in each phase (e.g., <10% charge imbalance). Thewaveform produces either a depolarizing or a hyperpolarizing nerve blockduring the first phase plateau, and in some cases also blocks during thesecond phase plateau. Increasing the current from zero to the plateau isoften performed slowly over the course of a few seconds in order toeliminate the generation of action potentials in the nerves.Additionally, multiple electrode contacts can be used to maintain aconstant conduction block by cycling between the different contacts todeliver the DC waveform to the nerve.

In still other instances, a DC waveform and the HFAC waveform can becombined to produce a nerve block with the desirable characteristics ofeach type of ENCB. The charge balanced DC can be established first andused to block the onset response from the HFAC, which typically lasts afew seconds. Once the onset response is complete, the charge balanced DCwaveform can be terminated (typically after charge balancing) and blockcan be maintained with the HFAC waveform.

Pain

ENCB can be used to treat both acute and chronic pain due to, forexample, cancer, pancreatitis, neuroma, endometriosis, post-herpeticneuralgia, back pain, headache, and joint replacement. In fact, the ENCBcan be used to block any nerve conduction leading to the perception ofpain as an alternative to neurolysis or chemical block. Notably, ENCB isreversible and can be used early in the treatment because if there areany side effects, they can be alleviated immediately by turning theblock off. Additionally, the intensity and extent of the ENCB can beadjustable (e.g., as an open loop system).

Depending on the pain treated with the ENCB, the electrode contacts canbe part of a cuff electrode, electrode contacts located near the targetnerve, a paddle-style electrode, a mesh-style electrode, or the like. Insome instances, the ENCB can be delivered to an autonomic nerve (e.g.,the sympathetic ganglia) as an alternative to blocking sensory nerves,which can produce a side effect of a dull buzzing sensation felt due tothe stimulation.

The ENCB can be accomplished through multiple methods. In someinstances, charge balanced or imbalanced HFAC waveforms (voltagecontrolled or current controlled) can be used to produce arapidly-induced and rapidly-reversible nerve conduction block. Typicalwaveform frequencies can be between 5 and 50 kHz. The waveform can becontinuous or interrupted, and each pulse can have a varied shape,including square, triangular, sinusoidal, or the like.

In other instances, charge balanced DC waveforms consisting of anincrease to a plateau of one polarity, which can last for a time period(e.g., 10 seconds), followed by a decrease of the current to an oppositepolarity, can be used for the ENCB. The plateaus of each phase can bethe same, but typically the second phase is 10-30% of the amplitude ofthe first phase. The total charge delivery is zero or substantially lessthan the charge in each phase (e.g., <10% charge imbalance). Thewaveform produces either a depolarizing or a hyperpolarizing nerve blockduring the first phase plateau, and in some cases also blocks during thesecond phase plateau. Increasing the current from zero to the plateau isoften performed slowly over the course of a few seconds in order toeliminate the generation of action potentials in the nerves.Additionally, multiple electrode contacts can be used to maintain aconstant conduction block by cycling between the different contacts todeliver the DC waveform to the nerve.

In still other instances, a DC waveform and the HFAC waveform can becombined to produce a nerve block with the desirable characteristics ofeach type of ENCB. The charge balanced DC can be established first andused to block the onset response from the HFAC, which typically lasts afew seconds. Once the onset response is complete, the charge balanced DCwaveform can be terminated (typically after charge balancing) and blockcan be maintained with the HFAC waveform.

Relaxation of the Urethral Sphincter

Reversible ENCB can be applied to produce a relaxation of the urinarysphincter on command (e.g., in an open loop system). An example of anapplication where this is important is in electrical stimulation systemsdesigned to produce bladder evacuation for individuals with spinal cordinjury. In these systems, stimulation of the sacral roots producesbladder contraction for evacuation, but also produces unwanted sphinctercontraction. The methods of the present disclosure can be appliedbilaterally to the pudendal nerve to prevent sphincter activity duringbladder activation. After the bladder is emptied, the block can beturned off to restore continence. The blocking electrode contact mayalso be used as stimulation to activate a weak sphincter and improvecontinence. Nerve conduction block on the sacral sensory roots can alsobe used to prevent spontaneous bladder contraction and thus improvecontinence. Methods can also be used to control bladder-sphincterdyssynergia in spinal cord injury.

Hyperhidrosis

Reversible ENCB can be applied to neural structures of the sympatheticnervous system (e.g., in an open loop system) to treat hyperhidrosis(sweaty palms). The ENCB is a reversible alternative to the traditionalsympathectomy, which involves a permanent surgical destruction ordisruption of fibers in the sympathetic chain. Sympathectomy ispermanent and may have irreversible side effects (like without anexcessive reduction leading to dry skin and other side effectsassociated with destruction of the sympathetic system). In contrast,ENCB can accomplish the same desirable effect without producing anypermanent damage to any neural structures. The ENCB can be applied whenneeded and/or adjusted so to provide a desired degree of reduction inpalmar sweating, without the undesirable side effects.

In one example, the ENCB can be applied to specific regions of thesympathetic nervous system. For example, the ENCB can be applied byelectrode contacts placed adjacent a targeted sympathetic ganglia sothat an electric field generated with sufficient intensity so that theaction potentials transmitted within or between sympathetic ganglia areblocked or down-regulated. In other instances, the ENCB can be appliedto by nerve cuff electrodes placed around the sympathetic chain (e.g.,around sympathetic fibers between ganglia, the sympathetic roots, or thesympathetic ganglia).

The ENCB can be accomplished through multiple methods. In someinstances, charge balanced or imbalanced HFAC waveforms (voltagecontrolled or current controlled) can be used to produce arapidly-induced and rapidly-reversible nerve conduction block. Typicalwaveform frequencies can be between 5 and 50 kHz. The waveform can becontinuous or interrupted, and each pulse can have a varied shape,including square, triangular, sinusoidal, or the like.

In other instances, charge balanced DC waveforms consisting of anincrease to a plateau of one polarity, which can last for a time period(e.g., 10 seconds), followed by a decrease of the current to an oppositepolarity, can be used for the ENCB. The plateaus of each phase can bethe same, but typically the second phase is 10-30% of the amplitude ofthe first phase. The total charge delivery is zero or substantially lessthan the charge in each phase (e.g., <10% charge imbalance). Thewaveform produces either a depolarizing or a hyperpolarizing nerve blockduring the first phase plateau, and in some cases also blocks during thesecond phase plateau. Increasing the current from zero to the plateau isoften performed slowly over the course of a few seconds in order toeliminate the generation of action potentials in the nerves.Additionally, multiple electrode contacts can be used to maintain aconstant conduction block by cycling between the different contacts todeliver the DC waveform to the nerve.

In still other instances, a DC waveform and the HFAC waveform can becombined to produce a nerve block with the desirable characteristics ofeach type of ENCB. The charge balanced DC can be established first andused to block the onset response from the HFAC, which typically lasts afew seconds. Once the onset response is complete, the charge balanced DCwaveform can be terminated (typically after charge balancing) and blockcan be maintained with the HFAC waveform.

Vertigo

Reversible ENCB can also be applied to the neural structures of theinner ear to treat vertigo. For example, vertigo can result fromMeniere's disease, which is a disorder of the inner ear (that can occurin one or both ears) causing spontaneous vertigo episodes.Traditionally, vertigo can be treated by sectioning the vestibularnerve, which involves identifying the vestibular nerve in the inner earand cutting the nerve while sparing the cochlear nerve, which runsadjacent to the vestibular nerve. Advantageously, ENCB can be used toproduce a similar effect, yet ENCB is fully reversible, which eliminatesany permanent side effects, including loss of hearing (which occurs inabout 20% of vestibular nerve sections). The ENCB can be appliedcompletely (e.g., controlled as a closed loop by one or more sensors oras an open loop by a physician) and continuously or episodically (e.g.,controlled as an open loop by the patient or physician) as needed to oneor both ears.

The ENCB can be delivered by electrode contacts placed distally to avoidblocking the cochlear nerve. Alternatively, a nerve cuff electrode canbe placed directly around the vestibular nerve branch to deliver theENCB, which allows for block of the entire vestibular nerve. Insulationaround the nerve cuff electrode prevents current spread to the adjacentcochlear nerve, preserving hearing during the block of the vestibularnerve. As another alternative, the nerve cuff electrode can be placedaround the entire vestibulocochlear nerve, and the ENCB can be appliedto reduce vertigo, but result in significant hearing loss. However, thehearing loss is only temporary since the ENCB is reversible.

The ENCB can be accomplished through multiple methods. In someinstances, charge balanced or imbalanced HFAC waveforms (voltagecontrolled or current controlled) can be used to produce arapidly-induced and rapidly-reversible nerve conduction block. Typicalwaveform frequencies can be between 5 and 50 kHz. The waveform can becontinuous or interrupted, and each pulse can have a varied shape,including square, triangular, sinusoidal, or the like.

In other instances, charge balanced DC waveforms consisting of anincrease to a plateau of one polarity, which can last for a time period(e.g., 10 seconds), followed by a decrease of the current to an oppositepolarity, can be used for the ENCB. The plateaus of each phase can bethe same, but typically the second phase is 10-30% of the amplitude ofthe first phase. The total charge delivery is zero or substantially lessthan the charge in each phase (e.g., <10% charge imbalance). Thewaveform produces either a depolarizing or a hyperpolarizing nerve blockduring the first phase plateau, and in some cases also blocks during thesecond phase plateau. Increasing the current from zero to the plateau isoften performed slowly over the course of a few seconds in order toeliminate the generation of action potentials in the nerves.Additionally, multiple electrode contacts can be used to maintain aconstant conduction block by cycling between the different contacts todeliver the DC waveform to the nerve.

In still other instances, a DC waveform and the HFAC waveform can becombined to produce a nerve block with the desirable characteristics ofeach type of ENCB. The charge balanced DC can be established first andused to block the onset response from the HFAC, which typically lasts afew seconds. Once the onset response is complete, the charge balanced DCwaveform can be terminated (typically after charge balancing) and blockcan be maintained with the HFAC waveform.

Sialorrhea

Sialorrhea or excessive drooling is a major issue in children withcerebral palsy and adjust with neurodegenerative disorders. Currentmedical management, using topical agents, oral agents, and botulinumtoxim, is unsatisfactory because these treatments are ineffective orproduce unwanted side effects, including lack of salivation whendesired. Advantageously, ENCB can be used as an alternative to thesetraditional treatments that can rapidly and reversibly block activationof the salivary glands, therefore reducing saliva production whendesired. The advantages of ENCB include the ability of a patient orcaregiver to turn on and of the activation of the salivary glands whendesired. Additionally, ENCB can provide for partial or incomplete block,reducing, but not eliminating, salivation, thereby alleviating thesymptoms without producing unwanted side effects.

ENCB for alleviation of sialorrhea can be applied to the nerve branchessupplying the autonomic activation of the salivary glands, targeting oneor more nerves. Alternatively, linear electrodes with one or morecontacts can be placed adjacent to the target nerves to produce thedesired block. This approach may simplify surgical installation. ENCBmay be applied directly to or near each salivary gland.

The ENCB can be accomplished through multiple methods. In someinstances, charge balanced or imbalanced HFAC waveforms (voltagecontrolled or current controlled) can be used to produce arapidly-induced and rapidly-reversible nerve conduction block. Typicalwaveform frequencies can be between 5 and 50 kHz. The waveform can becontinuous or interrupted, and each pulse can have a varied shape,including square, triangular, sinusoidal, or the like.

In other instances, charge balanced DC waveforms consisting of anincrease to a plateau of one polarity, which can last for a time period(e.g., 10 seconds), followed by a decrease of the current to an oppositepolarity, can be used for the ENCB. The plateaus of each phase can bethe same, but typically the second phase is 10-30% of the amplitude ofthe first phase. The total charge delivery is zero or substantially lessthan the charge in each phase (e.g., <10% charge imbalance). Thewaveform produces either a depolarizing or a hyperpolarizing nerve blockduring the first phase plateau, and in some cases also blocks during thesecond phase plateau. Increasing the current from zero to the plateau isoften performed slowly over the course of a few seconds in order toeliminate the generation of action potentials in the nerves.Additionally, multiple electrode contacts can be used to maintain aconstant conduction block by cycling between the different contacts todeliver the DC waveform to the nerve.

In still other instances, a DC waveform and the HFAC waveform can becombined to produce a nerve block with the desirable characteristics ofeach type of ENCB. The charge balanced DC can be established first andused to block the onset response from the HFAC, which typically lasts afew seconds. Once the onset response is complete, the charge balanced DCwaveform can be terminated (typically after charge balancing) and blockcan be maintained with the HFAC waveform.

Intractable Hiccups

ENCB can be used to mitigate intractable hiccups where by blockingphrenic nerve conduction. For example, an impending hiccup can be sensedthrough a nerve signal recording on the proximal phrenic nerve. A largevolley of activity, indicating an impending hiccup, can be used totrigger the ENCB more distally on the phrenic nerve. In certainembodiments, the block is only applied for a very brief period in orderto block the hiccup, and thus not interfering with normal breathing. TheENCB can include, for example, a DC waveform (through an electrodecontact of a high intensity material) followed by an HFAC waveform.

The foregoing description and examples have been set forth merely toillustrate the invention and are not intended as being limiting. Forexample, ENCB can be used to treat other disorders, such ascomplications of asthma (opening closed airways) or Parkinson's disease.Each of the disclosed aspects and embodiments of the present disclosuremay be considered individually or in combination with other aspects,embodiments, and variations of the disclosure. Further, while certainfeatures of embodiments of the present disclosure may be shown in onlycertain figures, such features can be incorporated into otherembodiments shown in other figures while remaining within the scope ofthe present disclosure. In addition, unless otherwise specified, none ofthe steps of the methods of the present invention are confined to anyparticular order of performance Modifications of the disclosedembodiments incorporating the spirit and substance of the disclosure mayoccur to persons skilled in the art and such modifications are withinthe scope of the present disclosure. Furthermore, all references citedherein are incorporated by reference in their entirety.

What is claimed is:
 1. A system comprising: a waveform generator togenerate an electrical nerve conduction block (ENCB); a controllercoupled with the waveform generator, wherein the controller isconfigured to receive an input comprising at least one parameter toadjust the ENCB; an electrical contact coupled with the waveformgenerator, wherein the electrical contact is configured to be placedinto contact with a nerve, wherein the electrical contact comprises ahigh charge capacity material that prevents formation of damagingelectro-chemical products at a charge delivered by the ENCB; wherein theelectrical contact is configured to deliver the ENCB to the nerve toblock transmission of a signal related to a pain through the nerve.
 2. Asystem according to claim 1, wherein the controller forms part of anopen loop control system.
 3. A system according to claim 2, wherein thecontroller is configured to receive the input to adjust the ENCB from auser.
 4. A system according to claim 1, wherein the controller formspart of a closed loop control system.
 5. A system according to claim 4,wherein the controller is configured to receive the input to adjust theENCB from an entity.
 6. A system according to claim 5, wherein theentity comprises a sensor configured to sense a change in aphysiological parameter.
 7. A system according to claim 2, wherein thecontroller is configured to interpret the input and configured to signalthe waveform generator including a parameter adjusted based on theinput.
 8. A system according to claim 7, wherein the waveform generatoris configured to generate an appropriate ENCB to be delivered to thenerve based on the adjusted parameter from the controller.
 9. A systemaccording to claim 1, wherein, based on the input, the controller isconfigured to specify a timing parameter, an intensity parameter, awaveform parameter so that an appropriate ENCB is generated.
 10. Asystem according to claim 1, wherein the ENCB comprises at least one ofa monophasic direct current (DC) waveform, a charge balanced directcurrent (CBDC) waveform, a substantially CBDC waveform, and a highfrequency alternating current (HFAC) waveform.
 11. A system according toclaim 1, wherein the waveform generator is configured to generatereversible ENCB so that when transmission of the ENCB is stopped, normalsignal transmission through the nerve is restored.